title: In vitro kinetic profiling of hepatitis C virus NS3 protease inhibitors by progress curve analysis.
abstract: Kinetic profiling of drug binding to its target reveals important mechanistic parameters including drug-target residence time. In this chapter, we focus on global progress curve analysis as a convenient method for kinetic profiling. Detailed guidelines with pros and cons for various experimental designs and data analysis are provided. Kinetic profiling of Boceprevir and Telaprevir is illustrated.
authors.affiliation: In Vitro Pharmacology, Merck Research Laboratories, Kenilworth, NJ, USA.
authors.forename: Rumin
authors.initials: R
authors.lastname: Zhang
authors.forename: William T
authors.initials: WT
authors.lastname: Windsor
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D057075:Enzyme Assays / Q000379:methods*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007700:Kinetics; D011480:Protease Inhibitors / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases